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June 26, 2017

Originally published in 2008, the underlying essence of a structure elucidation process is to structurally distinguish an unknown from a set of possible isomers. This is evident by the number of possible isomers for a given molecular formula.

The chart below divides isomers into three groups: Structural/Constitutional/Regio, Spin and Stereo/Spatial isomers. Wikipedia links are included for further reading into the different isomer classifications.

August 29, 2016

This manuscript covers various exercises of using a free CASE (computer-assisted structure elucidation) software application "Structure Elucidator". The purpose of these exercises is to use elucidation software to quickly explore potential candidates given a set of NMR data and a molecular formula. The learning process is similar to learning to use a mathematical calculator for a math problem. The software is available for free to all via a webpage link. The software comes with 112 exercises but we focus on three specific examples in the manuscript. The exercises focus on interpretation of 1H and 13C chemical shifts, identifying fragments and using process of elimination to explore hundreds of isomers in a matter of minutes.

The special feature was published in the journal Magnetic Resonance in Chemistry on August 2016 entitled "The fundamentals behind solving for unknown molecular structures using computer-assisted structure elucidation".

April 06, 2016

There are many variants of 1H-13C HSQC experiments that can used for elucidating unknown molecules. In particular, band-selective HSQC data can assist with the data interpretation of correlations with regions exhibiting ambiguous assignments.1

For the following unknown compound, two 1H -13C HSQC spectra were collected. Both datasets (bsgHSQC and gHSQC) were processed with the same set of parameters (F2: window function square sine bell 13.33 Hz at 0.075 s, zerofill to 4k, F1: window function gaussian 12.24 Hz, zerofill to 1k, FLP 256 pts). The band-selective gradient HSQC experiment was collected with less scans and yet the 1JHC could be clearly linked to the respective 13C signals along the F1 axis.

A special thanks goes to John Lowe, Catherine Lyall and Dave Carbery, University of Bath, UK.

October 07, 2015

In collaboration with Sequoia Sciences Inc., we developed a strategy for the dereplication of a complete or a partial structure using 1H NMR, 1H–13C HSQC and 1H–1H COSY spectral data, a molecular formula composition range and structural fragments against a massive database of about 22 million compounds is considered. The work was based on 18 compounds and was applicable to research on natural products and synthetic compounds.

June 19, 2015

From 2012 to 2015, I had the privilege to be involved in two collaborations aimed at elucidating 3 novel unknown compounds. The goals of both projects were to solve the three unknowns: two natural products and a synthetic product. I used a Computer-Assisted Structure Elucidation (CASE) software to explore thousands of isomers to find the best candidates.

Two natural products were elucidated and published in the journal Organic Letters on June 2015 entitledComputer-Assisted Structure Elucidation of Black Chokeberry (Aronia melanocarpa) Fruit Juice Isolates with a New Fused Pentacyclic Flavonoid Skeleton.http://pubs.acs.org/doi/ipdf/10.1021/acs.orglett.5b01284

For the following known compound, the 1H -13C HSQC-DEPT spectrum (collected at 150 Hz coupling constant) below shows a negative correlation (blue) at 2.72 and 61.1 ppm with a 1H integral of 1.0. The correlation is attributed to the terminal alkyne CH group. One expects the correlation to have a positive phase and thus appear red in colour. Herein, the spectrum shows a correlation of the opposite phase as a result of the high C-H coupling (~250 Hz). In some cases, the C-H coupling from alkyne group can be weak or missing.

December 10, 2013

A key step in being a successful elucidator is to understand the principles behind the experiment. Below is one such case.

For the following known compound, the 1H -13C HSQC-DEPT (or multiplicity-edited HSQC) spectrum (collected at 150 Hz coupling constant) below shows a negative correlation (blue) at 2.72 and 61.1 ppm with a 1H integral of 1.0. How would you assign this correlation?

October 25, 2013

An HMBC experiment correlates atoms over a longer range from 2-4 bonds. However, it can also exhibit correlations for 1-bond separation.

For a pure, unknown compound, the 1H -13C HMBC spectrum below shows three correlations to the carbon at 42 ppm. The correlations at 3.50 and 4.05 ppm correlate the 1H signal at 3.75 ppm as 1-bond separation for a CH group. The 1H signal at 3.46 ppm correlates as a long range 2-4 bond separation.

September 20, 2013

An HMBC experiment can be a key part in solving for an unknown compound. In this puzzle, 'extra' correlations add an extra degree of difficulty to its interpretation.

For a pure, unknown compound, the 1H -13C HMBC spectrum below shows three correlations to the carbon at 42 ppm. Can you interpret how the correlations at 4.05, 3.50 and 3.46 ppm should be assigned to the 1H signals 3.75 and 3.50 ppm?